The inner fluctuations of the brain in presymptomatic Frontotemporal Dementia: The chronnectome fingerprint

Genetic FTD Initiative, GENFI, Enrico Premi, Vince D. Calhoun, Matteo Diano, Stefano Gazzina, Maura Cosseddu, Antonella Alberici, Silvana Archetti, Donata Paternicò, Roberto Gasparotti, John van Swieten, Daniela Galimberti, Raquel Sanchez-Valle, Robert Laforce, Fermin Moreno, Matthis Synofzik, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James RoweRik Vandenberghe, Elizabeth Finger, Fabrizio Tagliavini, Alexandre de Mendonça, Isabel Santana, Chris Butler, Simon Ducharme, Alex Gerhard, Adrian Danek, Johannes Levin, Markus Otto, Giovanni Frisoni, Stefano Cappa, Sandro Sorbi, Alessandro Padovani, Jonathan D. Rohrer, Barbara Borroni

Research output: Contribution to journalArticlepeer-review

Abstract

Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a “chronnectome” approach (recurring, time-varying patterns of connectivity) to evaluate measures of dynamic connectivity in 472 at-risk FTD subjects from the Genetic Frontotemporal dementia research Initiative (GENFI) cohort. We considered 249 subjects with FTD-related pathogenetic mutations and 223 mutation non-carriers (HC). Dynamic connectivity was evaluated using independent component analysis and sliding-time window correlation to rs-fMRI data, and meta-state measures of global brain flexibility were extracted. Results show that presymptomatic FTD exhibits diminished dynamic fluidity, visiting less meta-states, shifting less often across them, and travelling through a narrowed meta-state distance, as compared to HC. Dynamic connectivity changes characterize preclinical FTD, arguing for the desynchronization of the inner fluctuations of the brain. These changes antedate clinical symptoms, and might represent an early signature of FTD to be used as a biomarker in clinical trials.

Original languageEnglish
Pages (from-to)645-654
Number of pages10
JournalNeuroImage
Volume189
DOIs
Publication statusPublished - Apr 1 2019

Keywords

  • C9orf72
  • Chronnectome
  • Dynamic brain functional connectivity
  • Frontotemporal dementia
  • Granulin
  • Microtuble associate protein tau
  • Mutation
  • resting-state fMRI

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience

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